Specific nephrotoxicity and cardiotoxicity of BT-CAL®, Sigma Anti-bonding Molecule Calcium Carbonate, in mice

Abstract

According to a high anti-osteoporotic efficacy of Sigma Anti-bonding Molecule Calcium Carbonate (SAC), repeated-dose toxicities of SAC were investigated to assess its feasibility as drug or functional food ingredient. Male ICR mice were given drinking water containing 0.006, 0.02 or 0.06% SAC for 4 weeks. SAC feeding decreased the body weights and feed and water consumptions of mice in a dose-dependent manner, especially, leading to severe emaciation and 70% death in 3 weeks in the high-dose (0.06%) group. Not only kidney and heart weights, but also the levels of blood urea nitrogen, creatinine, aspartate transaminase, and creatine phospokinase significantly increased after SAC administration, indicative of nephrotoxicity and cardiotoxicity. Such renal and cardiac toxicities were also confirmed by microscopic findings, exhibiting renal crystals and cardiac fibrosis, which may be due to the insoluble crystal formation and calcium overload, respectively. In conclusion, it is suggested that no observed adverse effect level of SAC is lower than 0.006% in mice, and that a long-term intake may cause serious adverse effects on renal and cardiac functions.